DTDM1: Dyslipidaemia and transcriptional dysregulation in DM1
Research type
Research Study
Full title
Exploring how transcriptional dysregulation may contribute to dyslipidaemia in Myotonic Dystrophy Type 1 (DM1)
IRAS ID
355064
Contact name
Emma Matthews
Contact email
Sponsor organisation
City St George's University of London - St George’s School of Health and Medical Sciences.
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Myotonic dystrophy type 1 (DM1) is the most common adult onset muscular dystrophy. It is caused by a CTG expansion in the 3’-untranslated region of the DMPK gene. The transcribed DMPK RNA containing this expanded region forms clusters which trap important splicing regulators e.g. MBNL1 within the cell nucleus. Splicing regulators like MBNL1 help to assemble genes in the correct way. Trapping them in the cell nucleus means there is a reduction in available splicing regulators. This in turn leads to mis-splicing (incorrect assembly) of numerous other genes in many different organs. For this reason DM1 doesn't just affect muscles but is a multi-systemic disorder. Clinical features include myopathy, myotonia, cardiac conduction defects or arrhythmias, cardiomyopathy, early onset cataracts, frontal balding, cognitive or intellectual disability and endocrine abnormalities including diabetes mellitus, thyroid disease and dyslipidaemia.
Most clinical features have been linked to mis-splicing of at least one relevant gene. Dyslipidaemia however has not. Dyslipidaemia can occur in people without DM1 and may be due to lifestyle factors e.g. sedentary behaviour. In DM1 there have been some small studies that found no difference between those who were more or less active and their lipid levels suggesting there are other reasons dyslipidaemia occurs. We currently don't know if dyslipidaemia in DM1 is due to genetic or lifestyle factors or a combination of the two.
In this study we will take blood from people with DM1. We will extract RNA from their blood and sequence it. We will compare this sequencing to sequencing from people without DM1 to see if genes involved in lipid metabolism are put together differently between those with and without DM1. We will also compare the results between those with DM 1 who have dyslipidaemia and those with normal lipid levels. At the same time, we will collect information from their medical records for demographics, level of mobility, co-morbidities e.g. diabetes to see if there is any correlation between these and lipid levels. We will also record events like heart attacks and strokes to see if they are increased by lipid levels in DM1.
This study aims to understand the causes of dyslipidaemia in DM1 in order to know how to best treat it. Identification of genetic pathways altering lipid levels may also show us targets for developing new lipid lowering treatments which may be applicable to the general population beyond DM1.REC name
South West - Frenchay Research Ethics Committee
REC reference
25/SW/0059
Date of REC Opinion
14 May 2025
REC opinion
Favourable Opinion